A widely-held vision arising from the Human Genome Project is use of newly available genetic information to guide preventive and therapeutic decision making in individual patients. One therapeutic area that seems particularly ripe to test this concept is pharmacogenomics, the idea that variability in therapeutic response includes a genomic component. Common variation in both germline and somatic tumor genes is an increasingly well-recognized contributor to variability in drug response, and as a result, recommendations for genotype-guided therapy are being promulgated. Through leadership in multiple genomic networks, Vanderbilt has been at the forefront of pharmacogenomic discovery and translation of this knowledge into clinical practice locally. However, few institutions or practitioners have the procedures and tools in place to incorporate genetic data into routine drug prescribing. In this proposal, we move toward this practice by establishing a program for integrating genomic medicine in diverse healthcare settings. The purpose of the Integrated, Individualized, and Intelligent Prescribing (I3P) project is to perform a multi-site demonstration that integrating genetic data within electronic health records (EHRs) can improve healthcare. We will establish the processes and infrastructure necessary to disseminate clinical genetic testing, results reporting, and decision support into diverse hospital and EHR environments. This application focuses on pharmacogenomics, given the role of adverse drug reactions (ADRs) as major causes of morbidity and mortality, the increasing number of recognized variants included in US Food and Drug Administration (FDA) labels as mediators of both efficacy and toxicity, and the relative lack of stigma attached to carriers of variants in pharmacogenes. The project will build on two ongoing, clinical genotyping efforts at Vanderbilt: 1) the Pharmacogenomic Resource for Enhanced Decisions In Care and Treatment (PREDICT) program, which prospectively tests patients for 184 high-value germline pharmacogenomic variants including those associated with clopidogrel, warfarin and simvastatin; and 2) the Personal Cancer Medicine Initiative (PCMI), which routinely performs multiplex tumor gene mutation testing in lung cancer and melanoma to direct therapy. I3P will leverage the existing expertise, informatics, and laboratory infrastructure and resources at Vanderbilt to implement genomic medicine in three diverse healthcare systems at early adopter sites. These healthcare systems include underserved, minority populations (Nashville General Hospital at Meharry Medical College), military populations (Nashville Veterans Affairs Medical Center), and a community health system (Aurora Health Care).